A facile direct route to N-(un)substituted lactams by cycloamination of oxocarboxylic acids without external hydrogen

Hu Li, Hongguo Wu, Heng Zhang, Yaqiong Su (Corresponding author), Y. Song (Corresponding author), Emiel Hensen (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Lactams are privileged in bioactive natural products and pharmaceutical agents and widely featured in functional materials. This study presents a novel versatile approach to the direct synthesis of lactams from oxocarboxylic acids without catalyst or external hydrogen. The method involves the in situ release of formic acid from formamides induced by water to facilitate efficient cycloamination. Water also suppresses the formation of byproducts. This unconventional pathway is elucidated by a combination of model experiments and density functional theory calculations, whereby cyclic imines (5‐methyl‐3,4‐dihydro‐2‐pyrrolone and its tautomeric structures) are found to be favorable intermediates toward lactam formation, in contrast to the conventional approach encompassing cascade reductive amination and cyclization. This sustainable and simple protocol is broadly applicable for the efficient production of various N‐unsubstituted and N‐substituted lactams.
Original languageEnglish
Pages (from-to)3778-3784
Number of pages7
JournalChemSusChem
Volume12
Issue number16
DOIs
Publication statusPublished - 22 Aug 2019

Keywords

  • amination
  • cyclization
  • density functional calculations
  • lactams
  • reduction

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